Oxidative damage is a major cause for replicative senescence and human aging. A person has 15,000 telomeres at birth but only 10,000 at age 20 and only 5,000 at age 65. External modulation of oxidative stress levels can modify telomere shortening rates and the replicative lifespan of a given cell culture. For example, hyperoxia (40% oxygen partial pressure) accelerates production of reactive oxygen species (ROS) of mitochondrial respiration and increases telomere shortening dramatically. Short telomeres activate a DNA-damage response that leads to apoptosis (programmed cell death) and senescence. As cells divide, short telomeres accumulate because of the end-replication problem. Short telomeres recruit DNA damage proteins that activate cellular programs of apoptosis or senescence. This cellular response manifests as organ failure in clinically recognizable syndromes of telomere shortening.
It would be desirable to develop treatments for beneficially altering programmed cell death (or modulating programmed cell life), which in turn may prolong the onset of disease, increase lifespan, and reverse the normal aging process in an individual.